Project Summary/Abstract Background. There is growing evidence that vitamin D may reduce the RISK of developing a cancer (including breast, colon, lung, and possibly prostate cancers). Results from animal and cellular experiments suggest that vitamin D may also affect the prognosis or outcome cancer AFTER diagnosis. Long Term Goals and Relevance to NCI Mission: The relationship between vitamin D and long-term head and neck cancer (HNC) outcomes has not been studied comprehensively. The long-term goal of this study is to analyze a well-annotated mature HNC dataset in hopes of finding strong associations to justify performing a prospective study of Vitamin D supplementation in HNC patients. Thus, this study meets NCI's mission to research interventions to improve health outcomes after cancer and its treatment as part of cancer survivorship research. Methods. We previously conducted a randomized controlled trial among 540 radiation treated HNC patients to test the effect of antioxidant vitamin supplementation, resulting in a long-term mature study of HNC outcomes. In this unique dataset of patients, the objectives of this study are to assess the relationships between HNC long-term outcomes and: (1) dietary intake (using a validated food frequency questionnaire) and serum level of vitamin D (measured using a radioimmunoassay on archived samples);and (2) genetic polymorphisms of key vitamin D-related genes involved either in the pharmacokinetics or pharmacodynamics of vitamin D. In addition (3), we will explore the relationships between the genetic polymorphisms of a larger set of vitamin D-related factors and HNC outcomes. We will study whether polymorphisms of genes that affect vitamin D's metabolism, transport, or function in the body also affect long-term HNC outcomes. Traditional statistical methods will be supplemented with bioinformatic approaches. The over-arching goal will be to identify associations between various vitamin D factors and HNC outcomes, taking into account known clinico-epidemiologic prognostic factors. PUBLIC HEALTH RELEVANCE: Project Narrative Relevance. Recently, Vitamin D has been found to be potentially influential in determining the prognosis or outcome of a number of cancers after diagnosis (most prior studies had evaluated Vitamin D in RISK of cancer, not PROGNOSIS). Dietary, genetic, and other factors may influence how the vitamin D pathway interacts with cancer. This application will comprehensively study the dietary, genetic and other influences of the Vitamin D pathway on head and neck cancer patient prognosis, with the goal of providing enough justification to develop a confirmatory clinical trial of Vitamin D supplementation in head and neck cancer patients.